The goal of this project is to develop and apply incisive, advanced but practical methods for analysis of spermatozoa, which can be used in the analysis and prediction of human fertility and its perturbations. The focus and orientation of this work are motivated by the need to apply such methods, in a standardized form, to the evaluation of hazards to human reproductive health that may arise in the environment or the workplace. The proposed studies have technological components which lead to new biostatistical methodologies which are applied to basic biomedical questions. The first Specific Aim consolidates, optimizes and then standardizes the machine vision technology (CASA-computer-aided sperm analysis) used to measure human sperm motion and morphology. It improves existing systems, by optimizing the accuracy, precision and biological relevance of the parameters which they measure. In so doing, it will provide computer codes and standard reference videotapes to all interested laboratories for calibration and quality control of any CASA system. The second and third Specific Aims apply the increased power of this newly developed technology to analysis of the relationship between human semen quality and fertility. The analytic strategy is not simply to characterize the semen of men whose fertility status is well-defined, but to develop new mathematical relationships which predict the likelihood of future fertility on the basis of parameters of present and past semen quality. Such relationships should prove to be more incisive tools for assessing the consequences of hazards to fertility than the traditional use of normative range for semen parameters. Three groups of men will be prospectively studied, and the results then integrated: normal men, representative of the general population, who abandon contraception and seek to conceive (Specific Aim 2); infertility patients who have abnormal semen by traditional standards (Specific Aim 3); and infertility patients who have traditionally normal semen (Specific Aim 3). The wives of the infertility patients will have been clinically assessed to have no apparent reproductive dysfunction. The fertility of all these men will be monitored, and the incidence of early spontaneous pregnancy loss will be determined for the first group. The results of Specific Aims 2 and 3 will have obvious application in the general assessment of human male fertility. They will also provide analytic tools, which can be immediately combined with the advanced but streamlined technology from Specific Aim 1, to applications in field studies of hazards to human fertility.